TY - JOUR
T1 - The systems biology simulation core algorithm
AU - Keller, Roland
AU - Dörr, Alexander
AU - Tabira, Akito
AU - Funahashi, Akira
AU - Ziller, Michael J.
AU - Adams, Richard
AU - Rodriguez, Nicolas
AU - Novère, Nicolas Le
AU - Hiroi, Noriko
AU - Planatscher, Hannes
AU - Zell, Andreas
AU - Dräger, Andreas
N1 - Funding Information:
The authors are grateful to B. Kotcon, S. Mesuro, D. Rozenfeld, A. Yodpinyanee, A. Perez, E. Doi, R. Mehlinger, S. Ehrlich, M. Hunt, G. Tucker, P. Scherpelz, A. Becker, E. Harley, and C. Moore, Harvey Mudd College, USA, for providing a Java implementation of Rosenbrock’s method, and to M. T. Cooling, University of Auckland, New Zealand, for fruitful discussion. The authors thank D. M. Wouamba, P. Stevens, M. Zwießele, M. Kronfeld, and A. Schröder for source code contribution and fruitful discussion. This work was funded by the Federal Ministry of Education and Research (BMBF, Germany) as part of the Virtual Liver Network (grant number 0315756). The Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology of Japan supported this work by Grants-in-Aid for Scientific Research on Innovative Areas (KAKENHI), grant number 23136513. In addition, this work was funded by the UK Biotechnology and Biological Sciences Research Council, grant number BB/D019621/1. We acknowledge support by the German Research Foundation (DFG) and the Open Access Publishing Fund of the University of Tuebingen.
PY - 2013/7/5
Y1 - 2013/7/5
N2 - Background: With the increasing availability of high dimensional time course data for metabolites, genes, and fluxes, the mathematical description of dynamical systems has become an essential aspect of research in systems biology. Models are often encoded in formats such as SBML, whose structure is very complex and difficult to evaluate due to many special cases.Results: This article describes an efficient algorithm to solve SBML models that are interpreted in terms of ordinary differential equations. We begin our consideration with a formal representation of the mathematical form of the models and explain all parts of the algorithm in detail, including several preprocessing steps. We provide a flexible reference implementation as part of the Systems Biology Simulation Core Library, a community-driven project providing a large collection of numerical solvers and a sophisticated interface hierarchy for the definition of custom differential equation systems. To demonstrate the capabilities of the new algorithm, it has been tested with the entire SBML Test Suite and all models of BioModels Database.Conclusions: The formal description of the mathematics behind the SBML format facilitates the implementation of the algorithm within specifically tailored programs. The reference implementation can be used as a simulation backend for Java™-based programs. Source code, binaries, and documentation can be freely obtained under the terms of the LGPL version 3 from http://simulation-core.sourceforge.net. Feature requests, bug reports, contributions, or any further discussion can be directed to the mailing list simulation-core-development at lists.sourceforge.net.
AB - Background: With the increasing availability of high dimensional time course data for metabolites, genes, and fluxes, the mathematical description of dynamical systems has become an essential aspect of research in systems biology. Models are often encoded in formats such as SBML, whose structure is very complex and difficult to evaluate due to many special cases.Results: This article describes an efficient algorithm to solve SBML models that are interpreted in terms of ordinary differential equations. We begin our consideration with a formal representation of the mathematical form of the models and explain all parts of the algorithm in detail, including several preprocessing steps. We provide a flexible reference implementation as part of the Systems Biology Simulation Core Library, a community-driven project providing a large collection of numerical solvers and a sophisticated interface hierarchy for the definition of custom differential equation systems. To demonstrate the capabilities of the new algorithm, it has been tested with the entire SBML Test Suite and all models of BioModels Database.Conclusions: The formal description of the mathematics behind the SBML format facilitates the implementation of the algorithm within specifically tailored programs. The reference implementation can be used as a simulation backend for Java™-based programs. Source code, binaries, and documentation can be freely obtained under the terms of the LGPL version 3 from http://simulation-core.sourceforge.net. Feature requests, bug reports, contributions, or any further discussion can be directed to the mailing list simulation-core-development at lists.sourceforge.net.
KW - Algorithms
KW - Biological networks
KW - Mathematical modeling
KW - Numerical integration
KW - Ordinary differential equation systems
KW - Simulation
KW - Software engineering
KW - Systems biology
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U2 - 10.1186/1752-0509-7-55
DO - 10.1186/1752-0509-7-55
M3 - Article
C2 - 23826941
AN - SCOPUS:84879801381
VL - 7
JO - BMC Systems Biology
JF - BMC Systems Biology
SN - 1752-0509
M1 - 55
ER -